Comparison of hemodynamic response functions obtained from resting-state functional MRI and invasive electrophysiological recordings in rats.

Resting-state functional MRI (rs-fMRI) is a popular technology that has enriched our understanding of brain and spinal cord functioning, including how different regions communicate (connectivity). But fMRI is an indirect measure of neural activity capturing blood hemodynamics. The hemodynamic response function (HRF) interfaces between the unmeasured neural activity and measured fMRI time series.

Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection.

Generating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it has other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides-with multiple mismatches to any natural sequence-that are tailored for desired properties around nucleic acid diagnostics. We find that MEA-designed guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared to guides derived directly from natural sequences, and illuminate interpretable design principles that broaden Cas13a targeting.

APPRAISE-AI Tool for Quantitative Evaluation of AI Studies for Clinical Decision Support.

Importance: Artificial intelligence (AI) has gained considerable attention in health care, yet concerns have been raised around appropriate methods and fairness. Current AI reporting guidelines do not provide a means of quantifying overall quality of AI research, limiting their ability to compare models addressing the same clinical question.

Objective: To develop a tool (APPRAISE-AI) to evaluate the methodological and reporting quality of AI prediction models for clinical decision support.

A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo.

The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O requirements.

A 128-channel receive array for cortical brain imaging at 7 T.

Purpose: A 128-channel receive-only array for brain imaging at 7 T was simulated, designed, constructed, and tested within a high-performance head gradient designed for high-resolution functional imaging.

Methods: The coil used a tight-fitting helmet geometry populated with 128 loop elements and preamplifiers to fit into a 39 cm diameter space inside a built-in gradient. The signal-to-noise ratio (SNR) and parallel imaging performance (1/g) were measured in vivo and simulated using electromagnetic modeling.

The confound of hemodynamic response function variability in human resting-state functional MRI studies.

Functional magnetic resonance imaging (fMRI) is an indirect measure of neural activity with the hemodynamic response function (HRF) coupling it with unmeasured neural activity. The HRF, modulated by several non-neural factors, is variable across brain regions, individuals and populations. Yet, a majority of human resting-state fMRI connectivity studies continue to assume a non-variable HRF.

Machine learning for cryosection pathology predicts the 2021 WHO classification of glioma.

Background: Timely and accurate intraoperative cryosection evaluations remain the gold standard for guiding surgical treatments for gliomas. However, the tissue-freezing process often generates artifacts that make histologic interpretation difficult. In addition, the 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular profiles in the diagnostic categories, so standard visual evaluation of cryosections alone cannot completely inform diagnoses based on the new classification system.

Improved psychosocial measures associated with physical activity may be explained by alterations in brain-gut microbiome signatures.

Obesity contributes to physical comorbidities and mental health consequences. We explored whether physical activity could influence more than metabolic regulation and result in psychological benefits through the brain-gut microbiome (BGM) system in a population with high BMI. Fecal samples were obtained for 16 s rRNA profiling and fecal metabolomics, along with psychological and physical activity questionnaires.

Ketone ester supplementation suppresses cardiac inflammation and improves cardiac energetics in a swine model of acute myocardial infarction.

Background: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a swine acute MI model.

Delivering the next generation of cancer immunotherapies with RNA.

Decades of oncologic clinical use have demonstrated that cancer immunotherapy provides unprecedented therapeutic benefits. Tragically, only a minority of patients respond to existing immunotherapies. RNA lipid nanoparticles have recently emerged as modular tools for immune stimulation.

Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients.

Histopathologic assessment is indispensable for diagnosing colorectal cancer (CRC). However, manual evaluation of the diseased tissues under the microscope cannot reliably inform patient prognosis or genomic variations crucial for treatment selections. To address these challenges, we develop the Multi-omics Multi-cohort Assessment (MOMA) platform, an explainable machine learning approach, to systematically identify and interpret the relationship between patients' histologic patterns, multi-omics, and clinical profiles in three large patient cohorts (n = 1888).

Contrast-Enhanced Cardiac Magnetic Resonance Imaging With a Manganese-Based Alternative to Gadolinium for Tissue Characterization of Acute Myocardial Infarction.

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium-based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast-enhanced magnetic resonance imaging.

RNA Delivery to Hematopoietic Stem and Progenitor Cells Targeted Lipid Nanoparticles.

Ex vivo autologous hematopoietic stem cell (HSC) gene therapy has provided new therapies for the treatment of hematological disorders. However, these therapies have several limitations owing to the manufacturing complexities and toxicity resulting from required conditioning regimens. Here, we developed a c-kit (CD117) antibody-targeted lipid nanoparticle (LNP) that, following a single intravenous injection, can deliver RNA (both siRNA and mRNA) to HSCs in rodents.

The 2022 RSV surge was driven by multiple viral lineages.

The US experienced an early and severe respiratory syncytial virus (RSV) surge in autumn 2022. Despite the pressure this has put on hospitals and care centers, the factors promoting the surge in cases are unknown. To investigate whether viral characteristics contributed to the extent or severity of the surge, we sequenced 105 RSV-positive specimens from symptomatic patients diagnosed with RSV who presented to the Massachusetts General Hospital (MGH) and its outpatient practices in the Greater Boston Area.

Pocket CLARITY enables distortion-mitigated cardiac microstructural tissue characterization of large-scale specimens.

Molecular phenotyping by imaging of intact tissues has been used to reveal 3D molecular and structural coherence in tissue samples using tissue clearing techniques. However, clearing and imaging of cardiac tissue remains challenging for large-scale (>100 mm) specimens due to sample distortion. Thus, directly assessing tissue microstructural geometric properties confounded by distortion such as cardiac helicity has been limited.

Translating Imaging Into 3D Printed Cardiovascular Phantoms: A Systematic Review of Applications, Technologies, and Validation.

Translation of imaging into 3-dimensional (3D) printed patient-specific phantoms (3DPSPs) can help visualize complex cardiovascular anatomy and enable tailoring of therapy. The aim of this paper is to review the entire process of phantom production, including imaging, materials, 3D printing technologies, and the validation of 3DPSPs. A systematic review of published research was conducted using Embase and MEDLINE, including studies that investigated 3DPSPs in cardiovascular medicine.

Partially Oxidized Alginate as a Biodegradable Carrier for Glucose-Responsive Insulin Delivery and Islet Cell Replacement Therapy.

Self-regulated insulin delivery that mimics native pancreas function has been a long-term goal for diabetes therapies. Two approaches towards this goal are glucose-responsive insulin delivery and islet cell transplantation therapy. Here, biodegradable, partially oxidized alginate carriers for glucose-responsive nanoparticles or islet cells are developed.

A soft robotic sleeve mimicking the haemodynamics and biomechanics of left ventricular pressure overload and aortic stenosis.

Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics and biomechanics of aortic stenosis.

Magnetic resonance imaging of cardiac metabolism in heart failure: how far have we come?

As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction. Cardiac metabolic imaging with magnetic resonance imaging (MRI) plays a crucial role in understanding the dynamic metabolic changes occurring in the failing heart, where the cardiac metabolism is deranged.